As it is known, Helicobacter pylori is a helix-shaped Gram-negative microaerophilic microorganism that can inhabit the stomach and the duodenum, adapting itself to the inhospitable environment of the gastric mucosa in a quite particular way, to the point that it often fails to produce any detectable symptoms. Actually, it is considered that more than 80% of the individuals infected with H. pylori are asymptomatic. Such microorganism infects more than half of the world population at the level of the gastro-duodenal tract. The transmission route of the infection has not been clarified, although infection seems to be typically acquired in the childhood.
The stomach is protected from its own gastric juice, made of concentrated hydrochloric acid and rich of digestive enzymes, by a thick layer of mucus which covers the gastric mucosa and within which the Helicobacter may penetrate and survive, resisting to the possible acid that may reach it thanks to an enzyme produced by such bacterium, urease. Urease converts the urea contained in large amounts in the stomach into bicarbonate and ammonium. Therefore, a basic environment Is established in the vicinity of the bacterial colony, such environment being capable of neutralizing the hydrochloric acid of gastric secretions, thereby protecting H. pylori. 
Another protective mechanism available to Helicobacter pylori consists in that the natural immune defenses of the body cannot reach it in the gastric mucus. The immune system reacts to the H. pylori infection by sending leukocytes, killer T lymphocytes and other defense factors, but these cannot reach the infection site, as they cannot easily penetrate through the mucus layer, and remain and accumulate in the site, leaving there their destructive content (consisting of superoxide radicals) when they die. Additional nutrients are sent on the site to assist the white blood cells, and this fact does no more than further feeding Helicobacter itself. As a result, a gastritis develops in a few days, which may sometimes progress up to peptic ulcer. In view of the foregoing, it is considered that the causative agent of the damage to the gastric mucosa is not H. pylori itself, but the inflammation and, consequently, the immune response to the microorganism.
From the scientific literature it appears that infection from Helicobacter pylori is the main cause of chronic gastritis and the most relevant factor for the development of peptic ulcer (Warren J R, Marshall B J. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983; 1:1273-5). By colonizing the stomach, H. pylori induces a persistent inflammation (chronic gastritis) which may last years without developing with clinical symptoms. However, in 10-20% of the cases, it may result in the development of gastric or duodenal ulcers.
Also gastric cancer (gastric adenocarcinoma and non-Hodgkin gastric lymphoma) is often associated with H. pylori (Moss S F. The carcinogenic effect of H. pylori on the gastric epithelial cell. J Physiol Pharmacol 1999; 50:847-56). In the frame of a wide review of cases of gastric carcinoma it has been shown that the presence of H. pylori results in a six-fold increase of the risk of gastric cancer. I is believed that chronic gastritis may lead to intestinal metaplasia, which in turn, may degenerate into malignant cancer. The low grade malignant lymphoma o MALToma, in turn, seems to derive from the malignant degeneration of lymphoid tissue associated with the mucosa. In this case, retrospective bioptic studies demonstrated that 90% of these MALTomes are associated he presence of H. pylori. 
The various strains of Helicobacter pylori are not endowed with the same pathogenic power: strains having in their chromosome an insertion defined “cag pathogenicity island” (cagPAI), a set of genes involved in the virulence of the microorganism, exhibit a higher inflammatory potential. About 50-70% of the H. pylori strains found in western countries contain the cag pathogenicity island, and the patients infected with bacteria containing the cag PAI have a stronger gastric inflammatory response and a higher risk of developing peptic ulcers or gastric cancer compared to patients infected with strains that do not contain such insertion in their genome. The cag-positive strains are able to inject in the colonized gastric cells an oncoprotein (codified by one the cag genes) named cagA, which increases the risk of developing neoplastic lesions (Censini S, Lange C, Xiang Z, Crabtree J E, Ghiara P, Borodovsky M, et al. cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci USA 1996; 93:14648-53).
Once the infection from Helicobacter pylori has been diagnosed in patients with peptic ulcer, the normal procedure consists in eradicating pharmacologically the microorganism, thus allowing the ulcer to heal. At present, the first choice standard treatment, known as “triple therapy” consists in the administration of:                a) a gastric proton pump inhibitor;        b) two antibiotics, selected from amoxicillin, clarithromycin, metronidazole or tetracycline.        
As it is known, the gastric proton pump is a metabolic mechanism typical of the stomach lining cells which allows them to secrete hydrochloric acid in the gastric juice. The gastric pump inhibitors are a group of molecules the main action of which is to reduce for a long term (from 18 to 24 hours) the acidity of gastric juice. They act through the inhibition of the gastric enzyme H+/K+-ATPase (the proton pump), i.e. the catalyst of the H+ and K+ ions exchange.
Such active ingredients, the most widespread of which are omeprazole, lansoprazole and esomeprazole, lead to a remarkable reduction of the gastric acidity, and are therefore used in the treatment of dyspepsia, gastro-oesophageal reflux and peptic ulcer, where they have practically replaced the drugs previously in use for similar indications, i.e. histamine H2 receptor antagonists or H2 anti-histamines, as ranitidine and cimetidine.
In the H. pylori eradication treatment, the proton pump inhibitors are used to alleviate the symptoms of peptic ulcer and to facilitate the actions of antibiotics, while the proper eradication action is carried out by the latter, which are administered with the precautions and limitations typical of any antibiotic treatment.
In the course of the years, the therapeutic protocols have progressively improved, allowing to go, in standard cases, from therapies of two weeks to therapies of 7 or 10 days, thus reducing the number of dosage units to be administered daily and limiting the toxicity and side effects of the same. Alternative protocols have been developed in case of allergies to specific drugs; second line treatment schedules have been designed in case of failure of the first cycle of therapy, and the overall eradication efficacy has improved, affording success rates of at least 80%. The case of undesired effects are kept within a limit of 10-15% of the patients, and normally such effects are not so serious to result in abandonment of the therapy.
Such undesired effects, both local and systemic, however, make the said therapy poorly tolerable. The most common of such side effects are, apart from cases of true intolerance to the active ingredient, dizziness and sense of confusion, oral bad taste, nausea and digestive or intestinal discomfort.
In addition, and more critically, an ever increasing number of patients appears to be infected by resistant bacteria: in most of the world several clarithromycin-resistant strains have been already evidenced, as well as metrodinazole-resistant strains. For the patients infected by resistant H. pylori strains the use of alternative antibiotics has been proposed, to be possibly exploited in case of failure of the first treatment cycle. For instance, for the treatment of clarithromycin-resistant strains the use of levofloxacin has been suggested, in a second-line triple therapy (Perna F, Zullo A, Ricci C, Hassan C, Morini S, Vaira D. Levofloxacin-based triple therapy for Helicobacter pylori re-treatment: role of bacterial resistance. Dig Liver Dis, 2007, 39(11):1001-5).
In the light of the foregoing, it is evident that pharmacological therapies for the eradication of Helicobacter pylori require continuous revision and updating, not only in order to improve the efficacy or tolerability of the drugs, but also as a consequence of the evolution of antibiotics-resistant strains in some populations, also depending on the use the various antibiotics in the different territories.
As recent studies have shown that the addition of substances having scavenging activity against free radicals, such as vitamin C, to the medicaments used to treat H. pylori infections improves the eradication rates, the interest of microbiologists and clinicians has concentrated on biologically active natural compounds, in particular plant extracts, known for being provided with antioxidant and/or antibacterial activity. The latter should be combined with the pharmacological therapies or should be used as nutritional supplements (Correa P, Malcom G, Schmidt B, Fontham E, Ruiz B, Bravo J C, et al. Antioxidant micronutrients and gastric cancer. Aliment Pharmacol Ther 1998; 1: 73-8). Several studies has shown the antibacterial effect of a wide variety of fruits and derivatives thereof, such as berries, garlic, onion, kiwi, citrus fruits and wine, as well as extracts from plant and drugs, in particular essential oils, cinnamon, thyme, propolis, licorice, paprika, tea and rice (see, for istance, Nostro A, Cellini L, Di Bartolomeo S, Di Campli E, Grande R, Cannatelli M A, et al. Antibacterial effect of plant extracts against Helicobacter pylori. Phytother Res 2005; 19:198-202; e Ohno T, Kita M, Yamaoka Y, Imamura S, Yamamoto T, Mitsufuji S, et al. Antimicrobial activity of essential oils against Helicobacter pylori. Helicobacter 2003; 8:207-15).
In such a frame, some of the present authors have recently studied and identified the phenolic compounds present in the thorn bush leaves (Rubus ulmifolius) and in the common wheat flour, and have ascertained the antioxidant activity and antibacterial power thereof against H. pylori strains (Martini S, D'Addario C, Colacevich A, Focardi S, Borghini F, Santucci A, Figura N, Rossi C. Antimicrobial activity against Helicobacter pylori strains and antioxidant properties of blackberry leale (Rubus ulmifolius) and isolated components. Int. J Antimicrob Agents. 2009; 34:50-9).
Amongst the phenolic components most abundantly present in such extracts there is ferulic acid, a lignin component making up the vegetal cell walls, that is largely found in rice, wheat and other cereals, as well as in coffee and in different seeds and fruits. The antioxidant properties of ferulic acid have led to propose its use in a wide variety of therapeutic applications for the prevention and treatment of pathologies ranging from cancer to neurodegenerative diseases, to diabetes, cardiovascular dysfunctions and also in the field of peptic ulcer and for the treatment of H. pylori infections, through several vegetal extracts containing it.
Considering the various further substances that have been proposed as active ingredients or adjuvants in the pharmacological treatment of Helicobacter pylori eradication in view of their antibacterial properties, the international patent application publ. No. WO 96/05822 (New England Medical Center Hospital) discloses the use of some molecules normally employed as non-ionic surfactants and emulsifiers, suitable for use in foods, cosmetics and pharmaceutical products, among which, specifically, polysorbates. Such compounds are a class of substances derived from polyethoxylated or PEG-ylated sorbitan ((3S)-2-(1,2-dihydroxyethyl)tetrahydrofuran-3,4-diol, a cyclic polyhydroxy compound obtained from the dehydration of sorbitol), having the four hydroxyl groups etherified with polyethylene glycol chains, in turn esterified with a fatty acid chain (monolaurate, monopamitate, monostearate or monooleate).
The polysorbates known with the commercial name Tween are often used in view of their solubilising properties as emulsifiers and antifoam additives in fermentations. Starting from experimentations on Helicobacter pylori cultures, the authors of the cited patent application have found that such compounds behave as potent inhibitors of bacterial growth. For such reasons the cited document proposes the administration of polysorbate-based compositions for the treatment of H. pylori infections in the frame of a sequential eradication treatment, wherein, however, any temporal overlapping between the antibiotic treatment and the treatment with polysorbate it is absolutely excluded.
As a matter of fact it had been found that the proposed surface active/emulsifying agents have bactericidal activity at some given concentrations, but only bacteriostatic activity at lower concentrations, and inhibit the H. pylori growth without totally eradicating it. Since many antibiotics used in clinics are active only on microorganisms being in an active growth phase, the simultaneous presence of the surface active/emulsifying agent proposed and the antibiotic would have been counterproductive. The therapy proposed by the cited document consists, therefore, in administering the known antibiotics for the treatment of Helicobacter in the absence of the proposed surfactant/emulsifying agent and, thereafter, administering such agent alone.
Also the international patent application publ. No, WO 97/36600 (AMBI Inc.), filed sometime later, proposes the use of polysorbates-containing compositions in the treatment of gastrointestinal disorders caused by H. pylori. The authors report to have found that polysorbates, in particular, non only inhibit H. pylori growth, but rapidly kill said bacterial strains, and therefore they may be used alone in the eradication of the microorganism. The cited document describes the use of polyoxyethilene sorbitan (and in particular polysorbate 20, which is the monolaurate ester of polysorbate) alone or in combination with other known antiulcer agents, including H2 receptor antagonists, bismuth salts, antacids and proton pump inhibitors and, specifically, in combination with mucolytic agents, but not in combination with systemic antibiotics. On the contrary, the administration together with antibiotics, which may be absorbed in the systemic circulation or pass through the intestine, is expressly not recommended.